Discovery of New 2-Phenylamino-3-acyl-1,4-naphthoquinones as Inhibitors of Cancer Cells Proliferation: Searching for Intra-Cellular Targets Playing a Role in Cancer Cells Survival.
(2023) Molecules — Vol. 28, n° 11, p. 4323 [1-23] (2023)
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- Authors
Benites, Julio 
Buc Calderon, Pedro
- Abstract
- A series of 2-phenylamino-3-acyl-1,4-naphtoquinones were evaluated regarding their in vitro antiproliferative activities using DU-145, MCF-7 and T24 cancer cells. Such activities were discussed in terms of molecular descriptors such as half-wave potentials, hydrophobicity and molar refractivity. Compounds and displayed the highest antiproliferative activity against the three cancer cells and were therefore further investigated. The in silico prediction of drug likeness, using pkCSM and SwissADME explorer online, shows that compound is a suitable lead molecule to be developed. Moreover, the expressions of key genes were studied in DU-145 cancer cells. They include genes involved in apoptosis (), tumor metabolism regulation (), redox homeostasis (), cell cycle regulation (), cell cycle progression (), epigenetic (), cell-cell communication () and inflammatory pathways (). Compound displays an interesting profile because among these genes, was significantly less expressed as compared to control conditions. Molecular docking shows that compound has good affinity with mTOR, unraveling a potential inhibitory effect on this protein. Due to the key role of mTOR on tumor metabolism, we suggest that impaired DU-145 cells proliferation by compound is caused by a reduced expression (less mTOR protein) and inhibitory activity on mTOR protein.
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Citations
Benites, J., Valderrama, J. A., Contreras, Á., Enríquez, C., Pino-Rios, R., Yáñez, O., & Buc Calderon, P. (2023). Discovery of New 2-Phenylamino-3-acyl-1,4-naphthoquinones as Inhibitors of Cancer Cells Proliferation: Searching for Intra-Cellular Targets Playing a Role in Cancer Cells Survival. Molecules, 28(11), 4323 [1-23]. https://doi.org/10.3390/molecules28114323 (Original work published 2023)